COAGULATION CHANGES UNDER THREE DIFFERENT DOSAGE REGIMENS OF SINGLE-CHAIN UROKINASE TYPE PLASMINOGEN ACTIVATOR

Therapy with streptokinase and urokinase induce effective thrombolysis but may be complicated by hemorrhagic side effects. In order to minimize these complications single-chain urokinase-type plasminogen activator (scu-PA) was given in patients with acute transmural myocardial infarction at three different dosage regimens consecutively in combination with heparin. In a first group four patients received 15 mg, thirteen 48 mg (group II) and five 72 mg (group III) of scu-PA intravenously. In 22 cases detailed clotting analyses could be performed. Results: The coagulation analysis demonstrated a reduction of the fibrinogen concentration by 11 % in group I, 17 % in group II and 44 % in group III. Plasminogen decreased by 9 % in the first, 43 % in the second and 61 % in the third group. The level of∝2-anti-plasmin showed a reduction of 12 % in group I, 48 % in group II and 80 % in group III. Fibrin degradation products increased in all groups. The euglobulin clot lysis time was moderately shortened in group I but significantly in the groups II and III. Reptilase and thrombin coagulase time were prolonged moderately. Thrombin clotting time and aPTT could be attained at therapeutic range by additional application of heparin. Antithrombin III showed no alteration. Thrombolysis could be achieved in none of the patients in group I but with good results in group II and III.

Our data suggest that intravenous application of scu-PA at a dosage of 48 mg is able to induce effective thrombolysis with only slight destruction of fibrinogen. At higher dosages a further increased rate of thrombolysis may be possible but also a higher rate of fibrinogenolysis may be considered.